Excessive Postoperative Bleeding Research Articles

Multiple Electrode Whole-Blood Aggregometry and Bleeding in Cardiac Surgery Patients Receiving Thienopyridines

Preoperative treatment with thienopyridines is associated with increased postoperative bleeding in cardiac surgery patients. Patients under treatment with thienopyridines have different levels of platelet dysfunction and the effects of discontinuation are not totally predictable. The present study aimed to determine if a preoperative assessment of platelet function in these patients could provide clinically relevant information regarding the risks of excessive postoperative bleeding and transfusion requirements. This is a retrospective analysis of prospectively collected data. Patients (n=87) under thienopyridine treatment until at least one week before cardiac surgery were enrolled in the study. Platelet function was assessed preoperatively with multiple electrode aggregometry: the adenosine diphosphate (ADP) test and TRAP (thrombin receptor-associated peptide) test were performed for all patients. Univariate analysis revealed that postoperative bleeding was associated (p<0.1) with preoperative serum creatinine level, platelet count, CPB (cardiopulmonary bypass) duration, and results from the ADP test and the TRAP test. Multivariable linear regression analysis confirmed the CPB duration (p=0.049) and ADP test (p=0.007) as independently associated with postoperative bleeding. The relationship between the ADP test and postoperative bleeding was investigated with polynomial regression analysis, and a logarithmic equation provided the best fit. The accuracy of prediction was good (area under the curve 0.71, p=0.013), with a cutoff value for the ADP test at 31 U (sensitivity 72%, specificity 66%, negative predictive value 92%, and positive predictive value 29%). The multiple electrode aggregometry ADP test in patients under thienopyridine treatment and undergoing cardiac surgery is associated with postoperative bleeding and platelet transfusion and provides an accurate preoperative prediction of postoperative bleeding risk.

Elective surgery in patients with congenital coagulopathies and inhibitors: experience of the National Haemophilia Centre of Venezuela

Elective surgery in patients with congenital haemophilia with inhibitors carries a high risk of bleeding. However, inhibitor patients also have a high risk of haemarthroses and other orthopaedic complications, and surgery could improve their quality of life. Successful elective surgery has been reported in inhibitor patients under haemostatic cover with plasma-derived activated prothrombin complex concentrate (pd-aPCC) or recombinant activated factor VII (rFVIIa). Recombinant FVIIa has recently become available in Venezuela and, unlike pd-aPCC, has not been associated with an anamnestic response. The aim of this study was to assess our experience using rFVIIa as a first-line and sustained treatment in elective invasive surgical procedures at the National Haemophilia Centre in Venezuela. Surgical procedures were classified as major or minor, under haemostatic cover with rFVIIa. A total of 13 patients (12 with haemophilia A with high-responding inhibitors and one with von Willebrand's disease type 3) underwent a total of 19 surgical procedures under rFVIIa cover. Thirteen procedures were classified as major surgeries. Intraoperative haemostasis was achieved in the majority of patients. Only two patients required an additional dose of rFVIIa, at 30 min and 75 min, respectively, with good results. Postoperative haemostasis was considered effective in 16 of 18 (89%) of the procedures in haemophilia A patients. Treatment was considered to be ineffective in two patients because of excessive postoperative bleeding. Data from the study provide no safety concerns, and demonstrate that rFVIIa provides effective haemostatic cover in elective surgery in patients with inhibitors; research is ongoing to determine the optimal dose for such procedures.

The need for intranasal packing in endoscopic endonasal surgery

Conclusion: The present findings indicate that conventional nasal packing is not required for endoscopic endonasal surgery. Objectives: To evaluate the routine use of packing in endoscopic endonasal surgery. Methods: From January 2006 through January 2009, 146 consecutive patients who underwent endoscopic endonasal surgery performed by the same surgeon in Kyoto University Hospital were evaluated. The surgical procedure was ended with conventional gauze packing in 70 consecutive patients from January 2006 through August 2007 (Packing group), and placing of oxidized cellulose on operative sites was performed in 76 consecutive patients from September 2007 to January 2009 (Non-packing group). We analyzed demographic characteristics, comorbidities, surgical procedures, incidence of packing the nose after excessive postoperative bleeding, and occurrence of postoperative adhesion. Results: No significant differences in the demographic characteristics, except for gender, and in comorbidities were found between the two groups. The number of endoscopic sinus surgery procedures with septoplasty and/or turbinoplasty, or tumor extirpation in the Non-packing group was significantly larger than that in the Packing group. There was no significant difference in the incidence of postoperative bleeding or postoperative adhesion between the two groups.

Von Willebrand disease and other bleeding disorders in women: consensus on diagnosis and management from an international expert panel

Reproductive tract bleeding in women is a naturally occurring event during menstruation and childbirth. In women with menorrhagia, however, congenital bleeding disorders historically have been underdiagnosed. This consensus is intended to allow physicians to better recognize bleeding disorders as a cause of menorrhagia and consequently offer effective disease-specific therapies.

Excessive Bleeding After Cardiac Surgery in Adults: Reasons and Management

Excessive Bleeding After Cardiac Surgery in Adults: Reasons and Management Postoperative bleeding is a concern for all patients undergoing cardiac surgery. In patients exposed to cardiopulmonary bypass, bleeding following surgery is excessive in up to twelve percent of patients in whom subsequent re-exploration is required. Several studies have evaluated main reasons, prevention of excessive postoperative bleeding and impact of patients outcomes. This article contains a literature review on excessive bleeding and re-exploration following cardiac surgery, main surgical and medical sources, prevention and management of bleeding.

Hemophilia a Carriers Experience Errors and Deficiencies in Care Leading to Emotional and Behavioral Responses That Could Further Compromise Their Care

Introduction Through previous studies and conferences, it was noted that medical errors perceived by haemophilia A (HA) carriers often resulted in poor relationships with health care providers (HCPs; principally physicians and nurses), and lead to reports of unfortunate and extreme emotional and behavioural responses. To explore the range medical experiences and responses of HA carriers, we undertook this qualitative study. M&M Interested members of the Canadian Haemophilia Society participated in semi-structured interviews. Nine adult interviewees (8 HA carriers, 1 non-carrier) discussed 11 carriers (7 adults, 4 children). A qualitative review exploring themes from anonymized interview transcripts was done using QSR NVIVO 8.0. Transcripts were coded for carrier symptoms, medical care experiences, perceived correctness of care, attitude of the caregiver, and emotional and behavioural responses.Results Nine of 11 carriers had experienced serious bleeds such as spontaneous bleeds, excessive post-operative or post-partum bleeding, or joint bleeds following mild to moderate trauma. Ten carriers had experienced symptoms of excess bleeding. All adult carriers reported heavy or prolonged menstrual bleeding. However, only 3 were reported as registered in a haemophilia treatment centre, and only one was regularly followed. Three carried factor first cards and four wore medic alert bracelets. 153 medical care experiences were discussed including 78 described as errors or deficiencies in care. HCP attitude was described as negative in 38 of 81 experiences. Interviewees felt that their concerns were trivialized, symptoms down-played, and they were not believed. In response, interviewees relayed deep feelings of disappointment, frustration, desperation, and complete loss of respect for the medical system. Other symptomatic carriers expressed self-doubt. Most often expressed was mistrust, disappointment, or loss of confidence in HCPs (8 of 9 interviewees, 46 instances), or anger (8 of 9 interviewees, 33 instances). Fear or anxiety was also commonly relayed (7 of 9 interviewees, 32 instances). Self-advocacy was the most common behavioural response (9 of 9 interviewees, 49 instances). Extreme behaviour included complete avoidance of the healthcare system (14 instances), and diagnosing and treating serious bleeds without medical supervision. Interviewees believed there was insufficient knowledge about bleeding disorders in women among HCPs (5 of 9 interviewees), insufficient knowledge about gynaecological norms among HCPs and patients (3 of 9), reticence of carriers to discuss personal gynaecological problems (2 of 9), and down-playing by carriers of their own symptoms as compared to more severely affected males (4 of 9). Interviewees often related errors in the care of family members and non-family members. Experiences shared within and among families affirmed their concepts of appropriate care and reinforced perceptions of inadequate care.Conclusions The bleeding disorder that affects HA carriers is a unique issue of women and children. HA carriers can experience serious bleeds and report numerous errors in medical management and negative attitudes toward their concerns. Their experiences often result in strong emotional responses, mistrust of the medical system, and some extreme and potentially detrimental behaviours. Solutions to these problems could include widely circulated management principles endorsed by both HCP and HA carrier groups, improved communication and education, registration of carriers in haemophilia treatment centres or women's bleeding disorder clinics, and improved communication with the wider haemophilia community to rebuild a positive relationship of trust with the medical care system.

Exodontia and Antiplatelet Therapy

The fear of excessive bleeding often prompts the physician to stop long-term, low-dose antiplatelet therapy before any surgical procedure. This may put the patient at risk of an adverse thromboembolic event. We undertook an assessment of the incidence of prolonged postoperative bleeding after dental extractions among patients on uninterrupted antiplatelet therapy, and evaluated the need to stop such medications before dental extractions. Eighty-two patients requiring dental extractions were included in this study, of whom 57 were on antiplatelet therapy (aspirin). Patients were divided into 3 groups. Group 1 consisted of patients in whom antiplatelet therapy was interrupted (n = 25), group 2 consisted of those continuing their medication (n = 32), and group 3 comprised healthy patients not on antiplatelet therapy (n = 25). Preoperative bleeding time and clotting time were determined in all patients. The surgical procedure involved single or multiple teeth extractions under local anesthesia with a vasoconstrictor. All patient groups were similar regarding age, gender distribution, dosage of antiplatelet drug, and medical condition for which the drug was prescribed. Events of single or multiple teeth extractions were also comparable among the 3 groups. Pressure packing was performed in all cases as in routine dental extractions. One-way analysis of variance was performed to determine the significance of prolonged bleeding among groups. The mean bleeding times in groups 1, 2, and 3 were 3 minutes, 2 minutes and 45 seconds, and 1 minute and 49 seconds, respectively. The mean clotting times in groups 1, 2, and 3 were 5 minutes and 4 seconds, 4 minutes and 52 seconds, and 3 minutes and 42 seconds, respectively. No patient in any group had any episode of prolonged or significant bleeding from the extraction sites. Local hemostasis had been satisfactorily obtained in all cases with the use of a pressure pack for 30 minutes. Routine dental extractions can be safely performed in patients on long-term antiplatelet medication, with no interruption or alteration of their medication. Such patients do not have an increased risk of prolonged or excessive postoperative bleeding.

Postoperative Bleeding in Retired Racing Greyhounds

Some retired racing Greyhounds (RRG) that undergo surgery bleed excessively. Greyhounds that bleed excessively will have one or more preoperative hemostatic abnormalities that can be used to predict the risk and severity of postoperative bleeding. Eighty-eight RRG undergoing ovariohysterectomy or castration. All dogs were evaluated preoperatively with a physical exam, CBC, platelet count, OSPT, APTT, platelet function with PFA-100(a); fibrinogen, d-dimer, plasminogen (Plmg), antiplasmin (AP), antithrombin (AT), and vWF concentration (vWF:Ag); vWF collagen binding assay (vWF:CBA), and Factor XIII assay. Assays were repeated in the dogs that bled, and in an age- and sex-matched control group of RRG. Twenty-six percent of the dogs had bleeding 36-48 hours after surgery. AP (P <.0001) and AT concentration (P= .007) were significantly lower, and vWF:CBA (P= .0284) was higher preoperatively in the dogs with excessive hemorrhage. A lower platelet count (P= .001) and hematocrit (P= .002), shorter OSPT (P= .0002) and higher plasma fibrinogen (P <.0001), and AP (P= .001) concentration were detected at the time of bleeding compared with preoperative values in the dogs that bleed excessively. The same findings were observed postoperatively for the control group, except for the decrease in hematocrit. The results indicate that this excessive postoperative bleeding is not attributable to a primary or secondary hemostatic defect, but could result from altered fibrinolysis.

Aprotinin—still courting controversy

Excessive postoperative bleeding during cardiac surgery calls for transfusions of allogeneic blood products, and up to 5% of patients undergoing coronary artery bypass grafting and 10% of those undergoing more complex heart surgery need early reoperation to control haemorrhage. Reoperation for bleeding increases hospital mortality and postoperative morbidity by three or four times, substantially increases hospital stay, and has a sizeable effect on health-care costs.

Purified antithrombin supplementation in coronary revascularisation operations

Background and objective: Purified antithrombin concentrates or human recombinant antithrombin have been proposed for treating heparin resistance in cardiac operations with cardiopulmonary bypass, and exert a beneficial effect in terms of haemostatic system activation control. However, little information is available with respect to antithrombin supplementation and clinical outcome in selected categories of patients. The aim of this study is to evaluate clinical outcome data in patients intraoperatively treated with purified antithrombin compared to a control population. Methods: 89 patients forming the AT-treated group received purified antithrombin to correct preoperatively low values of antithrombin activity or to treat heparin resistance. The Control group was retrospectively created with a propensity score analysis. After verifying the homogeneity of the two groups, various outcome variables were compared between groups. Results: Patients in the AT-treated group had a shorter Intensive Care Unit (2.6 ± 3 vs. 3 ± 2.7 days) and Hospital (7.5 ± 3.5 vs. 8.6 ± 4.5 days) stay, and a lower rate (relative risk 0.1, 95% confidence interval 0.01-0.81) of severe postoperative morbid events. Conversely, they demonstrated a significant, albeit clinically irrelevant, more pronounced postoperative bleeding tendency. Conclusions: AT supplementation in patients at risk for inadequate thrombin suppression during the operation reduces postoperative complications and shortens the recovery time. However, a careful monitoring of the heparin requirements is recommended in order to avoid an undesired excessive postoperative bleeding.

Impact of Sonoclot hemostasis analysis after cardiopulmonary bypass on postoperative hemorrhage in cardiac surgery

The Sonoclot Analyzer provides a functional test of whole blood coagulation by measuring the viscous property of the blood sample. In this study, we used a modified Sonoclot assay, using cuvettes with a glass bead activator containing heparinase, and compared the Sonoclot data before and after cardiopulmonary bypass (CPB) to assess the usefulness in predicting postoperative hemorrhage. In 41 cardiac surgery patients, Sonoclot data were obtained immediately after heparin administration (pre-bypass) and just before protamine administration (post-bypass). Excessive bleeding was defined as chest tube drainage greater than 2 ml.kg(-1).h(-1) in 1 h during the first 4 h after surgery. There were no significant differences in Sonoclot values before and after CPB in patients with acceptable bleeding (n = 29). In patients with excessive bleeding (n = 12), Sonoclot variables reflecting fibrin formation (activated clotting time [ACT], rate of fibrin formation [clot rate], and peak clot signal) were preserved after CPB; however, the variables reflecting platelet-fibrin interaction (time to peak, peak angle, and clot retraction rate) were significantly different from their respective pre-bypass values. Sonoclot analysis showed impairment of clot maturation after CPB in patients with excessive postoperative bleeding. Our results suggest that abnormal postoperative hemorrhage can be predicted by Sonoclot analysis with a new glass bead-activated heparinase test performed after CPB.

Platelet dysfunction after normothermic cardiopulmonary bypass in children: Effect of high-dose aprotinin

Platelet dysfunction after cardiopulmonary bypass (CPB) can contribute to excessive post-operative bleeding. Most trials of the protective effect of aprotinin in this setting have involved hypothermic CPB, which is more deleterious for platelets than normothermic CPB. Here we investigated the effect of aprotinin on platelet function during normothermic CPB in pediatric patients. Twenty patients (9 newborns [<1 month old] and 11 infants [<36 month old]), weighting less than 15 kg and undergoing normothermic CPB (35-36 degrees C) were randomly assigned to two equal groups, one of which received high-dose aprotinin. Platelet function was assessed by flow cytometry just before CPB and 5 minutes after heparin neutralization. F1 + 2 fragments were measured by ELISA before and 5 minutes after CPB. Platelet activation marker expression (CD62P and activated alphaIIbbeta3) induced by ADP or TRAP was lower after CPB than before CPB, suggesting a deleterious effect of normothermic CPB on platelet function. Prothrombin fragment F1 + 2 levels increased after CPB. Aprotinin administration did not influence the level of prothrombin fragments or platelet marker expression measured in basal condition. However, after CPB, the capacity for platelet activation was higher in the aprotinin group, as shown by measuring CD62P expression after TRAP activation (p = 0.05). This study suggests that pediatric normothermic CPB causes platelet dysfunction, and that high-dose aprotinin has a protective effect.

Perioperative Management of a Heterozygous Carrier of Glanzmann’s Thrombasthenia Submitted to Coronary Artery Bypass Grafting With Cardiopulmonary Bypass

Glanzmann's thrombasthenia is a congenital hemorrhagic disorder transmitted as an autosomal recessive trait and characterized by altered production and/or assembly of the platelet membrane glycoprotein IIb/IIIa receptor. We describe the perioperative management of a heterozygous carrier of Glanzmann's thrombasthenia submitted to cardiac surgery with cardiopulmonary bypass and the case was complicated by early excessive postoperative bleeding.

Hemodilution and surgical hemostasis contribute significantly to transfusion requirements in patients undergoing coronary artery bypass

We sought to determine the incidence of and risk factors for the development of low intraoperative hematocrit levels and of excessive postoperative bleeding in patients undergoing coronary artery bypass grafting, whether the risk factors are the same, and their effect on blood product transfusions. We performed a prospective cohort study of 613 adult patients who underwent coronary artery bypass grafting in 3 tertiary, university-affiliated hospitals during the period from October 1, 2000, to March 31, 2001. Low intraoperative hematocrit levels (<19%) were found in 131 (24%) patients who had operations performed with extracorporeal circulation compared with in 3 (4%) patients with operations performed off pump. In multivariate analysis this was associated with older age, female sex, lower preoperative hemoglobin levels, lower body surface area, longer duration on bypass, and use of higher total volumes with more hydroxyethyl starch in the circuit. Low intraoperative hematocrit levels did not predict excessive postoperative hemorrhage (>1 L of mediastinal drainage in the first 12 hours). This occurred in 26% (n = 140) of patients undergoing on-pump operations and in 25% of patients undergoing off-pump operations and in multivariate analysis was associated with male sex, longer pump times, not receiving aprotinin, and operations performed by certain surgeons but not with total circuit or hydroxyethyl starch volume. We observed that the risk factors for the development of a low intraoperative hematocrit level and excessive postoperative bleeding differed. Our results suggest that decreasing these outcomes in patients undergoing cardiac surgery requires a comprehensive approach, including limiting hemodilution, particularly in female subjects with lower preoperative hemoglobin levels, and careful attention to surgical hemostasis.

Major surgery in a severe haemophilia A patient with high titre inhibitor: use of the thrombin generation test in the therapeutic decision

Summary. In haemophilia patients with inhibitor, elective orthopaedic surgery is usually performed under recombinant activated factor VII (rFVIIa). We report here the case of a severe haemophilia A patient with a high inhibitor who needed a bilateral total knee arthroplasty. Recombinant FVIIa was previously shown to be ineffective for the treatment of muscle and joint bleedings, and he had a history of excessive postoperative bleeding under activated prothrombin complex concentrate (APCC). Thrombin generation test (TGT) was used to assess the efficacy of Factor Eight Inhibitor Bypassing Activity (FEIBA). Insufficient correction of thrombin-generating capacity was observed after administration of 75 U kg(-1) FEIBA. In a multidisciplinary environment, a bilateral total knee arthroplasty was performed using a protocol combining immunoadsorption of inhibitors preoperatively associated with FVIII replacement during a first phase followed by FEIBA when the inhibitor reappeared. To our knowledge this is the first direct application of TGT in the management of haemophilia patients with inhibitor, which indicated that a sequential use of immunoadsorption, FVIII and FEIBA was the most appropriate treatment to perform this major elective surgery. This case demonstrates that this combined protocol can be safely used to cover major surgery in inhibitor patients. In addition, it also suggests that TGT may have a major contribution in the decision-making process of the most adapted therapy for the treatment of such high-risk patients.

Perioperative Monitoring of Primary and Secondary Hemostasis in Coronary Artery Bypass Grafting

On-pump cardiac surgery is accompanied by complex alterations of hemostasis. The excessive postoperative bleeding has been attributed to acquired platelet dysfunction, impaired plasmatic coagulation, and increased fibrinolysis. The characterization of the hemostatic defects responsible for bleeding is crucial for specific treatment and optimal clinical management of the patient. For rapid determination of platelet-dependent primary hemostatic capacity (PHC), the Platelet Function Analyzer PFA-100 system is available. To evaluate the PFA performance in perioperative monitoring, a study was performed in 49 patients selected for low bleeding risk undergoing selective primary coronary artery bypass grafting (CABG). We compared PHC with Simplate bleeding time (BT) and platelet aggregometry. Furthermore, we analyzed global hemostasis by thromboelastography (TEG) and plasmatic coagulation by standard clotting tests prothrombin time (PT, Quick), activated partial thromboplastin time (aPTT), thrombin time (TT) and clotting factors and fibrinolysis by batroxobin (reptilase) time (RT). In all patients BT was postoperatively increased by 1.5- to 2-fold irrespective of perioperative complications and decreased to mildly prolonged values on the first postoperative day (1st day). In patients without complications, PHC in both collagen-adenosine diphosphate closure time (CADP-CT: 83 seconds preop, 78 seconds postop, and 74 seconds 1st day) and collagen-epinephrine closure time (CEPI-CT: 98 seconds preop, 95 seconds postop, 85 seconds 1st day) remained nearly stable. Apart from a patient with postoperative moderate thrombocytopenia, in bleeding patients no other significant defect of postoperative platelet hemostatic capacity was observed. However, on 1st day, the PHC of those patients was significantly reduced compared with non-bleeding patients. In patients with postoperative myocardial ischemia, increased PHC was identified by significantly shorter postoperative CADP-CT (66 seconds vs. 83 seconds) than in uncomplicated patients. By aggregometry, partial platelet dysfunction was observed in some patients without correlation to bleeding complications. In seven of 9 patients the postoperative bleeding complication was attributed to prolonged heparin anticoagulation and/or mildly enhanced fibrinogenolysis/fibrinolysis by TEG and standard plasmatic coagulation tests (TEG: k time 18 minutes vs. 8 minutes; aPTT: 47 seconds vs. 32 seconds; TT: 18.0 seconds vs. 12.3 seconds) and (RT: 19.5 seconds vs. 17.7 seconds). The impairment of PHC, platelet aggregation, and clotting factors observed on the 1st day in bleeding and in intra-aortic balloon pump (IABP) patients are most likely secondary effects, for example, loss of active platelets and clotting factors, to the primary postoperative bleeding or implantation of the IABP. In conclusion, our data indicate that in standard CABG procedures highly variable alterations of the hemostatic system occur after cardiopulmonary bypass (CPB) even in patients with assumed low operative risks. For identification of post-CPB bleeding complications, thromboelastography, aPTT, and TT and heparin and batroxobin (reptilase) time as fibrinolysis-sensitive assays are useful. Platelet function appears to be rapidly restored in uncomplicated CABG. PHC determination by PFA-100 demonstrates a high specificity for adequate platelet function and, therefore, could be beneficial in improved transfusion of platelet concentrates. PHC testing by PFA-100 may help identify postoperative platelet hyper-reactivity associated with myocardial lesion.

Bleeding Indicators and Wound Complications with Ximelagatran and Warfarin after TKR: Findings from 3 Clinical Trials.

Introduction: Prophylaxis of venous thromboembolism (VTE) in patients undergoing total knee replacement (TKR) most often entails anticoagulation, yet minimization of excessive postoperative bleeding and wound complications is critical to attain an excellent functional result. Ximelagatran (Exanta®, AstraZeneca), the first oral alternative to warfarin, has a rapid onset of action and requires no coagulation monitoring or dose adjustment. Three randomized, double-blind trials of VTE prophylaxis after TKR comparing ximelagatran 24 and 36 mg BID with well-controlled warfarin (target INR 2.5) were completed: Study 236 (n=680), EXULT A (n=2301), and EXULT B (n=2303). When administered for 7–12 days, ximelagatran 36 mg BID was superior to well-controlled warfarin, while 24 mg yielded numerically better but not statistically superior efficacy over warfarin. Adjudicated bleeding rates did not differ significantly.Objective: To assess the postoperative bleeding complications and overall surgical wound appearance during anticoagulation after TKR.Methods: Two comparison pools were created: 36-mg pool (ximelagatran 36 mg and corresponding warfarin groups from EXULT A and B) and 24-mg pool (ximelagatran 24 mg and corresponding warfarin groups from Study 236 and EXULT A). Bleeding indicators, i.e., postoperative wound drainage, bleeding index, and transfusion requirements, were compared. A prespecified subjective assessment of the surgical wound was performed on postoperative Day 3, end of treatment (Day 7–12), and at follow-up (4–6 weeks). If wound appearance was rated “worse than expected” at any time point, wound characteristics of swelling, drainage, erythema, and bleeding were assessed. Intra-articular bleeding, unusual bruising or hematoma, and bleeding requiring an intervention were also recorded. Results:36-mg Pool (n=3810)24-mg Pool (n=2178)Bleeding IndicatorsXimelagatranWarfarinXimelagatranWarfarinPost-op wound drainage, mean in mL (95% CI)697 (675, 718)704 (682, 725)659 (632, 686)654 (626, 682)Bleeding Index, mean (95% CI)3.4 (3.3, 3.4)3.3 (3.2, 3.4)3.2 (3.1, 3.3)3.1 (3.0, 3.2)TransfusionsUnplanned, % of Pts8.98.1Not AssessedNot AssessedTotal, % of Pts33.533.637.634.3Vol. Transfused/Pt, mean (95% CI)630 mL (602, 659)606 mL (578, 635)1.7 U (1.6, 1.8)1.7 U (1.6, 1.8)Overall wound appearance (worse than expected), %9.28.78.98.2Wound characteristics (worse than expected)Swelling, %5.14.55.74.6Drainage, %3.62.42.71.8Erythema, %3.93.72.83.5Bleeding, %1.71.2Not AssessedNot AssessedIn the 36- and 24-mg pools the wound was assessed as “expected” or “better than expected” for ≥90% of the patients in the ximelagatran and warfarin groups. For the small number of patients with “worse than expected” wounds, the differences between the ximelagatran and warfarin groups were not statistically significant. Bleeding complications of the surgical wound, including intra-articular bleeding (<3.5%), unusual bruising or hematoma (<5.0%), and bleeding requiring an intervention (<0.9%), were few and comparable between treatment groups.Conclusions: Analysis of bleeding indicators and complications of the surgical wound revealed no significant differences between treatment groups, supporting the safety of 36 mg for all patients undergoing TKR.

Can extra protamine eliminate heparin rebound following cardiopulmonary bypass surgery?

Abstract Objectives Heparin rebound, the reappearance of anticoagulant activity after adequate neutralization with protamine, is thought to contribute to excessive postoperative bleeding after cardiac surgery. We have previously demonstrated that a significant amount of heparin is bound nonspecifically to plasma proteins and is incompletely neutralized by protamine. The aim of this study was to investigate whether clinically important bleeding attributable to heparin rebound can be eliminated by infusion of small amounts of additional protamine for 6 hours postoperatively and whether this treatment can reduce mediastinal blood loss. Methods Three hundred patients undergoing elective cardiac surgery were randomized to receive either a continuous infusion of protamine sulphate (25 mg/h for 6 hours) postoperatively or saline placebo. Serial blood samples were obtained to measure thrombin clotting time and anti-factor Xa activity. Heparin bound nonspecifically to plasma proteins was measured after displacement with a chemically altered heparin with low affinity to antithrombin. Mediastinal blood loss and transfusion requirements were recorded. Results Heparin rebound was demonstrated in every patient in the placebo group as reflected by increased thrombin clotting time, anti-factor Xa activity, and protein-bound heparin between 1 and 6 hours after surgery. In contrast, heparin rebound was eliminated in the protamine infusion group. The thrombin clotting time was normalized and both heparin concentration and protein-bound heparin were almost undetectable ( P Conclusions Postoperative protamine infusion was able to almost totally abolish heparin rebound. In the context of this study, protamine infusion resulted in reduced postoperative bleeding but the magnitude was insufficient to alter transfusion requirements.

Investigation of Blood Compatibility and Determination of Clinical Performance of PMEA Coated and Flow Optimized Oxygenator

In this study, the blood compatibility of the tip-to-tip coated and flow-optimized extracorporeal circuits were investigated using poly(2-methoxyethylacrylate) PMEA-coated oxygenators and tubing sets. Total protein, human serum albumin, fibrinogen, erythrocyte, leukocyte and platelets loss quantities were analyzed on blood samples withdrawn five different times during cardiopulmonary bypass (CPB) such as: baseline (T1), during CPB (T2), end of CPB (T3), after protamine injection (T4) and intensive care (T5), no fibrinogen loss was observed for the tip-to-tip coated system. After an operation, protein desorption assays from fiber surfaces of the tip-to-tip coated and flow-optimized extracorporeal circuits showed very little desorption. Less protein desorption was found between sonicated fibers and fiber sample solutions at &lt;0.2mg/dL and 0.58mg/dL, respectively. For tip-to-tip coated and flow-optimized extracorporeal system, no platelet aggregation and no erythrocyte, leukocyte losses were observed. Optimized flow path and eliminated straight turns due to integration of exchangers minimized turbulent flows. Larger surface areas of the fibers optimized blood flow speed and improved gentle flow conditions and lowered shear stress. Clinically, no excessive postoperative bleeding was observed by the patients with the tip-to-tip coated system after 24 hours (hemorrhage was 387mL). The average unit of red blood cell and fresh frozen plasma transfusions were 0.98 and 2.10 units, respectively. Differences in adsorbed HSA on the hollow fiber surfaces were examined by STM which indicated that less protein existed on the sample solution of the non-sonicated fiber surfaces.

Can extra protamine eliminate heparin rebound following cardiopulmonary bypass surgery?

Objectives Heparin rebound, the reappearance of anticoagulant activity after adequate neutralization with protamine, is thought to contribute to excessive postoperative bleeding after cardiac surgery. We have previously demonstrated that a significant amount of heparin is bound nonspecifically to plasma proteins and is incompletely neutralized by protamine. The aim of this study was to investigate whether clinically important bleeding attributable to heparin rebound can be eliminated by infusion of small amounts of additional protamine for 6 hours postoperatively and whether this treatment can reduce mediastinal blood loss. Methods Three hundred patients undergoing elective cardiac surgery were randomized to receive either a continuous infusion of protamine sulphate (25 mg/h for 6 hours) postoperatively or saline placebo. Serial blood samples were obtained to measure thrombin clotting time and anti-factor Xa activity. Heparin bound nonspecifically to plasma proteins was measured after displacement with a chemically altered heparin with low affinity to antithrombin. Mediastinal blood loss and transfusion requirements were recorded. Results Heparin rebound was demonstrated in every patient in the placebo group as reflected by increased thrombin clotting time, anti-factor Xa activity, and protein-bound heparin between 1 and 6 hours after surgery. In contrast, heparin rebound was eliminated in the protamine infusion group. The thrombin clotting time was normalized and both heparin concentration and protein-bound heparin were almost undetectable ( P < .001). There was a modest 13% reduction in postoperative bleeding but this did not reduce blood transfusions. No adverse events were attributable to the extra protamine. Conclusions Postoperative protamine infusion was able to almost totally abolish heparin rebound. In the context of this study, protamine infusion resulted in reduced postoperative bleeding but the magnitude was insufficient to alter transfusion requirements.